Pyridine carboxylates, aqueous reactions

Poly(methyl 3-(l-oxypyridinyl)siloxane) was synthesized and shown to have catalytic activity in transacylation reactions of carboxylic and phosphoric acid derivatives. 3-(Methyldichlorosilyl)pyridine (1) was made by metallation of 3-bromopyridine with n-BuLi followed by reaction with excess MeSiCl3. 1 was hydrolyzed in aqueous ammonia to give hydroxyl terminated poly(methyl 3-pyridinylsiloxane) (2) which was end-blocked to polymer 3 with (Me3Si)2NH and Me3SiCl. Polymer 3 was N-oxidized with m-ClC6H4C03H to give 4. Species 1-4 were characterized by IR and H NMR spectra. MS of 1 and thermal analysis (DSC and TGA) of 2-4 are discussed. 3-(Trimethylsilyl)-pyridine 1-oxide (6), l,3-dimethyl-l,3-bis-3-(l-oxypyridinyl) disiloxane (7) and 4 were effective catalysts for conversion of benzoyl chloride to benzoic anhydride in CH2Cl2/aqueous NaHCC>3 suspensions and for hydrolysis of diphenyl phosphorochloridate in aqueous NaHCC>3. The latter had a ti/2 of less than 10 min at 23°C. 

The oxidative effects of silver(II) complexes of pyridine carboxylates have been studied for a variety of substrates. With ar-amino acids, a rapid reaction occurred at 70 °C in aqueous solution with bis(pyridyl-2-carboxylato)silver(II). 4 The product was the next lower homologous aldehyde and yields were generally greater than 80%. Other substrates included primary and secondary amines, alcohols, monosaccharide derivatives, alkenes, arylalkanes and arylalkanols.90 Only minor differences were detected in efficiencies when 2-, 3- or 4-mono-, or 2,3-di-carboxylates were used as the oxidant. 

The reaction between acyl halides and alcohols or phenols is the best general method for the preparation of carboxylic esters. It is believed to proceed by a 8 2 mechanism. As with 10-8, the mechanism can be S l or tetrahedral. Pyridine catalyzes the reaction by the nucleophilic catalysis route (see 10-9). The reaction is of wide scope, and many functional groups do not interfere. A base is frequently added to combine with the HX formed. When aqueous alkali is used, this is called the Schotten-Baumann procedure, but pyridine is also frequently used. Both R and R may be primary, secondary, or tertiary alkyl or aryl. Enolic esters can also be prepared by this method, though C-acylation competes in these cases. In difficult cases, especially with hindered acids or tertiary R, the alkoxide can be used instead of the alcohol. Activated alumina has also been used as a catalyst, for tertiary R. Thallium salts of phenols give very high yields of phenolic esters. Phase-transfer catalysis has been used for hindered phenols. Zinc has been used to couple... 

Unsymmetrical as well as symmetrical anhydrides are often prepared by the treatment of an acyl halide with a carboxylic acid salt. The compound C0CI2 has been used as a catalyst. If a metallic salt is used, Na , K , or Ag are the most common cations, but more often pyridine or another tertiary amine is added to the free acid and the salt thus formed is treated with the acyl halide. Mixed formic anhydrides are prepared from sodium formate and an aryl halide, by use of a solid-phase copolymer of pyridine-l-oxide. Symmetrical anhydrides can be prepared by reaction of the acyl halide with aqueous NaOH or NaHCOa under phase-transfer conditions, or with sodium bicarbonate with ultrasound. 

Unlike the case of the Ni-catalyzed reaction, which afforded the branched thioester (Eq. 7.1), the PdCl2(PPh3)3/SnCl2-catalyzed reaction with 1-alkyne and 1-alkene predominantly provided terminal thioester 6 in up to 61% yield in preference to 7. In 1983, a similar hydrothiocarboxylation of an alkene was also documented by using a Pd(OAc)2/P( -Pr)3 catalyst system with t-BuSH to form 8 in up to 79% yield (Eq. 7.6) [16]. It was mentioned in the patent that the Pt-complex also possessed catalyhc activity for the transformation, although the yield of product was unsatisfactory. In 1984, the hydrothiocarboxylation of a 1,3-diene catalyzed by Co2(CO)g in pyridine was also reported in a patent [17]. In 1986, Alper et al. reported that a similar transformation to the one shown in Eq. (7.3) can be realized under much milder reaction conditions in the presence of a 1,3-diene [18], and the carboxylic ester 10 was produced using an aqueous alcohol as solvent (Eq. 7.7) [19]. 

Carboxy-2-pyridylthio)propionic acids, prepared by the reaction of 2-mercatopyridin-3-carboxylic acid with 3-bromopropionic acid in aqueous KOH, undergo cyclization upon treatment with anhydrous sodium acetate and acetic anhydride to afford 2,3-dihydrothiopyrano[2,3-3]pyridin-4(4//)-ones. These products undergo further reaction with phenylhydrazine to give the phenylhydrazone (isolated) and then Fischer indole cyclization to give novel 5/7,1177-pyrido[2, 3 2,3]thiopyrano[4,3-3]indoles <2000JHC379>. 

Pyridine is not polarographically reducible in aqueous solvents but in aprotic media, such as acetonitrile,211 DMF,212 or liquid ammonia,213 it is reduced at rather negative potentials to the anion-radical, which then dimerizes. Some electron-attracting substituents, notably carboxyl derivatives, render the nucleus reducible even in aqueous solvents. Quaternary derivatives are generally reducible. JV-Alkylpyridinium ions thus give a free radical, which dimerizes rapidly the radical was trapped by a-phenyl-Af-tert-butylnitrone.214 1,3-Dimethylpyridinium ion is reduced in buffered aqueous medium to a 4,4 -dimer, which undergoes further chemical reaction, possibly an addition of water to one of the double bonds of the 1,4-dihydropyridine rings.215... 

In another synthesis using a preformed pyridine derivative a cyanoacetic acid ester is condensed in a Guareschi-type reaction with an a-substituted /3-keto carboxylic acid ester and an amine to give a hydroxypyridone (18 Scheme 3). These compounds are suitable precursors for an acid catalyzed cyclization to furo[2,3-6]pyridine-6-ones (19). N-Substituted derivatives may also be prepared by this route (64AP754). The aqueous solutions of these furopyridines show an intensive blue fluorescence. 

The p-sulfanyl amides 28 are synthesized from N-protected amino acids 24 via amino alcohols 25, which are converted into (5-acetylsulfanyl amides 26 by a Mitsunobu reaction. The (5-amine disulfide 27 is subsequently coupled with a variety of carboxylic acids, followed by reduction with tributylphosphine in aqueous THF in the presence of pyridine to produce the free thiol 28 (Scheme 5).1211 Detailed experimental procedures for these compounds have not been reported. 

In a different sequence of reactions, N-acetylation of 274 and exposure of the intermediate imide 275 to ethanolic KOH gave a mixture (about 2 1) of the desired carboxylic acid 276 together with the starting lactam 274 via the non-selective hydrolysis of the imide moiety of 275 (148a,c). When 276 was treated with /V-bromosuccinimide (NBS), an intermediate bromolactone was produced which was heated at reflux in pyridine in the presence of DBU to give 277. The conversion of the lactone 277 to the lactam 278 was effected by heating 277 in aqueous NaOH followed by protection of the resulting allylic alcohol function as a tetrahydropyranyl ether. 

In the event, iodolactonization of the carboxylate salt derived from the ester 458 afforded 459, and subsequent warming of the iodo lactone 459 with aqueous alkali generated an intermediate epoxy acid salt, which suffered sequential nucleophilic opening of the epoxide moiety followed by relactonization on treatment with methanol and boron trifluoride to deliver the methoxy lactone 460. Saponification of the lactone function in 460 followed by esterification of the resulting carboxylate salt with p-bromophenacylbromide in DMF and subsequent mesylation with methanesulfonyl chloride in pyridine provided 461. The diazoketone 462 was prepared from 461 by careful saponification of the ester moiety using powdered potassium hydroxide in THF followed by reaction with thionyl chloride and then excess diazomethane. Completion of the D ring by cyclization of 462 to the keto lactam 463 occurred spontaneously on treatment of 462 with dry hydrogen chloride. 

To a stirred suspension of p-(p-methoxybenzyloxy)-phenylmalonic acid (125 mg) in methylene chloride (3 ml) are added triethylamine (55 I) and oxalyl chloride (26 I) at -15°C, and the suspension is stirred for 40 minutes at 0°C. The mixture is added to a solution of diphenylmethyl 7p-amino-7a-methoxy-3-(l-methyltetrazol-5-yl)thiomethyl-l-oxadethia-3-cephem-4-carboxylate (100 mg) in methylene chloride (3 ml) and pyridine (63 I), and the mixture is stirred for 30 minutes at 0°C. The reaction mixture is diluted with ethyl acetate, washed with aqueous 2N-hydrochloric acid and water, dried over sodium sulfate, and concentrated to give crude product (212 mg), which is chromatographed on silica gel (20 g) and eluted with a mixture of ethyl acetate and acetic acid (99 1) to give diphenylmethyl-7p-[a-p-(p-methoxybenzyloxy)phenyl-a-carboxyacetamido]-7a-methoxy-3-(l-methyltetrazol-5yl)thiomethyl-l-oxadethia-3-cephem-4-carboxylate as foam (71 mg). Yield 45%. 

In 2004, excellent yields of hydroperoxides 91 and 92 were obtained (>95%) in the photooxidation of racemic acid 90 (Scheme 11.17) [96]. The diastereoselectivity of the photooxidation favored the trans-configured products due to the anti-directing effect of the protonated carboxylic acid group. Regioselectivity favored the formation of 92 over 91. Pyridine helped to accelerate the deprotonation of the CH next to COOH of 90, affording 92, and also suppressed the formation of aromatic compounds which otherwise would take place in the absence of pyridine. A great many studies of ene reactions have been conducted in organic solvents [97-101] or aqueous media [102-106] one such report appeared which used a fluorous biphasic solution [107]. 

Amino acyl adenylates are obtained in the reaction of adenosine 5-phosphate (ASP) with free amino acids in aqueous pyridine, mediated by DCC. The linkage is an anhydride between the amino acid carboxyl group and the phosphate in A5P." ... 

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